CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations

Gunnlaugur P. Nielsen, Karen L. Burns, Andrew Rosenberg, David N. Louis

Research output: Contribution to journalArticle

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Abstract

Osteosarcomas often suffer mutations of the RB (retinoblastoma) gene, with resultant inactivation of the pRb protein. pRb is one component in a cell-cycle control pathway that includes the p16 (encoded by the CDKN2A gene) and cyclin-dependent kinase 4 (cdk4, encoded by the CDK4 gene) proteins. We therefore sought to determine whether the CDKN2A and CDK4 genes were altered in those osteosarcomas that lacked RB inactivation. Twenty-one osteosarcomas (2 low-grade and 19 high-grade) were evaluated for homozygous deletion of the CDKN2A gene, CDK4 amplification, and allelic loss of the RB gene, as well as for expression of p16 and pRb proteins. Five high-grade osteosarcomas showed loss of p16 expression; four of these had homozygous CDKN2A deletions, and the fifth had a probable deletion obscured by numerous nonneoplastic, p16- immunopositive multinucleated giant cells. Thus, p16 immunohistochemistry may provide a sensitive means for assessing CDKN2A status. Twelve tumors (including the two low-grade osteosarcomas) were immunopositive for pRb, and nine tumors were immunonegative for pRb. Of the five cases with CDKN2A/p16 alterations, none had allellic loss of the RB gene and all expressed pRb, suggesting that each of these tumors had an intact RB gene. None of the tumors showed CDK4 amplification. No alterations were detected in the two low-grade osteosarcomas. This study suggests that CDKN2A is a tumor suppressor inactivated in osteosarcomas that lack RB mutations and that the p16-pRb cell-cycle control pathway is deregulated in a large number of high- grade osteosarcomas.

Original languageEnglish
Pages (from-to)159-163
Number of pages5
JournalAmerican Journal of Pathology
Volume153
Issue number1
StatePublished - Jul 1 1998
Externally publishedYes

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p16 Genes
Retinoblastoma
Gene Deletion
Osteosarcoma
Retinoblastoma Genes
Neoplasms
Cell Cycle Checkpoints
Cyclin-Dependent Kinase 4
Mutation
Proteins
Gene Amplification
Loss of Heterozygosity
Giant Cells
Immunohistochemistry

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. / Nielsen, Gunnlaugur P.; Burns, Karen L.; Rosenberg, Andrew; Louis, David N.

In: American Journal of Pathology, Vol. 153, No. 1, 01.07.1998, p. 159-163.

Research output: Contribution to journalArticle

Nielsen, Gunnlaugur P. ; Burns, Karen L. ; Rosenberg, Andrew ; Louis, David N. / CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations. In: American Journal of Pathology. 1998 ; Vol. 153, No. 1. pp. 159-163.
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